Device and method for converting direct current into alternate current

The device for converting direct current into alternate current comprises a multilevel converter associated with at least a source of direct current and a modulation unit having piloting means for piloting the converter for the conversion of the direct current into an alternate output current, in which the modulation unit comprises comparison means for comparing the output current value with a preset positive threshold value and a preset negative threshold value, the piloting means being suitable for piloting the converter with a pulse modulation of the unipolar type in the event of the output current value being above the positive threshold value or below the negative threshold value and with a pulse modulation of the complementary type in the event of the output current value being below the positive threshold value and above the negative threshold value. The method for converting direct current into alternate current comprises a piloting phase of a multilevel converter for the conversion of a direct voltage into an alternate output voltage, a comparison phase of the output current value with a preset positive threshold value and a preset negative threshold value, the piloting phase being suitable for piloting the converter with a pulse modulation of the unipolar type in the event of the output current value being above the positive threshold value or below the negative threshold value and with a pulse modulation of the complementary type in the event of the output current value being below the positive threshold value and above the negative threshold value

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) Inhibits Na+/K+-ATPase and Ras Oncogene Activity in Cancer Cells

The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12a) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12b) displayed ∼10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na(+)/K(+)-ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prognostic nutritional index predicts toxicity in head and neck cancer patients treated with definitive radiotherapy in association with chemotherapy

Background: The Prognostic Nutritional Index (PNI) is a parameter of nutritional and inflammation status related to toxicity in cancer treatment. Since data for head and neck cancer are scanty, this study aims to investigate the association between PNI and acute and late toxicity for this malignancy. Methods: A retrospective cohort of 179 head and neck cancer patients treated with definitive radiotherapy with induction/concurrent chemotherapy was followed-up (median follow-up: 38 months) for toxicity and vital status between 2010 and 2017. PNI was calculated according to Onodera formula and low/high PNI levels were defined according to median value. Odds ratio (OR) for acute toxicity were calculated through logistic regression model; hazard ratios (HR) for late toxicity and survival were calculated through the Cox proportional hazards model. Results: median PNI was 50.0 (interquartile range: 45.5\u201353.5). Low PNI was associated with higher risk of weight loss > 10% during treatment (OR = 4.84, 95% CI: 1.73\u201313.53 for PNI 10% and late mucositis. Conclusions: PNI could help clinicians to identify patients undergoing radiotherapy who are at high risk of acute and late toxicity

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication.

BACKGROUND: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. PATIENTS AND METHODS: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. RESULTS: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). CONCLUSIONS: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Prognostic significance of neutrophil‐to‐lymphocyte ratio in HPV status era for oropharyngeal cancer

Aim: To evaluate the role of baseline neutrophil-to-lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status. Patients and methods: A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age >18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed. Results: Seventy-seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow-up was 50 months. A value of NLR 653 was associated with poorer OS. Two-year OS was 91% and 81% in pts with NLR <3 and 653, respectively. Conclusion: A baseline NLR 65 3 at treatment initiation represented a negative prognostic marker for OPC treated with definitive CRT. These results are in line with literature data, and prognostic value of NLR has been confirmed restaging our cohort with new TNM staging (8th ed.). Therefore, NLR could be considered a valuable biomarker for risk stratification in pts with OPC